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Prostaglandin I 2 , indomethacin, and heparin promote postischemic neuronal recovery in dogs
Author(s) -
Hallenbeck J. M.,
Leitch D. R.,
Dutka A. J.,
Greenbaum L. J.,
McKee A. E.
Publication year - 1982
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410120204
Subject(s) - heparin , anesthesia , medicine , ischemia , prostaglandin
Forty‐five conditioned male mongrel dogs were exposed to multifocal ischemia sufficient to maintain suppression for 60 minutes of the P 1 –N 1 amplitude of the cortical sensory evoked response (CSER), a quantifiable index of neuronal function. Ischemia was induced and regulated by successive embolization of 20 to 50 μl increments of air via the right internal carotid artery. Subsequently, the P 1 –N 1 amplitude recovery of the CSER was followed for an additional 15, 60, or 120 minutes while the dogs were treated or left untreated. The combination of prostaglandin I 2 (PGI 2 ), indomethacin, and heparin promoted a statistically significant augmentation of return of CSER amplitude relative to no treatment, PGI 2 alone, indomethacin alone, PGI 2 and heparin, indomethacin and heparin, or PGI 2 and indomethacin. After 60 minutes of recovery, animals receiving combined PGI 2 , indomethacin, and heparin achieved a 57% recovery of P 1 –N 1 amplitude relative to baseline, while the corresponding recoveries in all other groups clustered around 20%. By 120 minutes of postischemic follow‐up, the CSER recovery induced by PGI 2 , indomethacin, and heparin was 80% compared to 17% in untreated animals. By 15 minutes into the recovery period, the combination of the three agents had eliminated very low flows in the “neuron‐disabling” range (defined as 0 to 15 ml/100gm/min for gray matter and 0 to 6 ml/100gm/min for white matter) in contrast to the relative inefficacy of no treatment or treatment with other than the triple combination of drugs. The study lends some support to a planned clinical trial of PGI 2 , indomethacin, and heparin in acute occlusive stroke in humans.